A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction.

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Research Abstract Details 

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A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Abstract Text:

Kevin Ogden,Janice M Thompson,Zachary Hickner,Taoying Huang,Dale D Tang,Stephanie W Watts,

Crk-associated substrate (CAS), a 130-kDa adaptor protein, was discovered as a tyrosine kinase substrate of Src that was important to cellular motility and actin filament formation. As the tyrosine kinase Src is utilized by the 5-hydroxytryptamine (5-HT)(2A) receptor in arterial contraction, we tested the hypothesis that CAS was integral to 5-HT(2A) receptor-mediated vasoconstriction. Rat thoracic aorta was used as a model of the arterial 5-HT(2A) receptor. Western and immunohistochemistry analyses validated the presence of CAS in the aorta, and tissue bath experiments demonstrated reduction of contraction to 5-HT (13.5 +/- 5% control maximum) and the 5-HT(2) receptor agonist alpha-methyl-5-HT (6 +/- 2% maximum) by latrunculin B (10(-6) mol/l), an actin disruptor. In aorta contracted with 5-HT (10(-5) mol/l), tyrosine phosphorylation (Tyr410) of CAS was significantly increased (approximately 225%), and both contraction and CAS phosphorylation were reduced by the 5-HT(2A/2C) receptor antagonist ketanserin (3 x 10(-8) mol/l). Src is one candidate for 5-HT-stimulated CAS tyrosyl-phosphorylation as 5-HT promoted interaction of Src and CAS in coimmunoprecipitation experiments, and the Src tyrosine kinase inhibitor PP1 (10(-5) mol/l) abolished 5-HT-induced tyrosyl-phosphorylation of CAS and reduced 5-HT- and alpha-methyl-5-HT-induced contraction. Antisense oligodeoxynucleotides delivered to the aorta reduced CAS expression (33% control) and arterial contraction to alpha-methyl-5-HT (45% of control), independent of changes in myosin light chain phosphorylation. These data are the first to implicate CAS in the signal transduction of 5-HT.

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Publishing Authors By Initials

K Ogden,JM Thompson,Z Hickner,T Huang,DD Tang,SW Watts,

For similar vasoconstriction research abstracts see: vasoconstriction research

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A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of physiology. Heart and circulat

VOLUME: 291

Page Numbers: H2857-63

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 21

MONTH: 07

YEAR: 2006

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901228

A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Keywords Mesh Terms:

KEYWORDS: Vasoconstriction

MESH TERMS: physiology

Chemical & Substance for Abstract: A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Information

Substance Name: latrunculin B

Registry Number: 76343-94-7

Grant and Affiliation Information for A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction.

AFFILIATION: Dept. of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-08115

ACRONYM: HL

MEDLINETA: Am J Physiol Heart Circ Physio

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